3'UTR C2370A allele of the IL-23 receptor gene is associated with relapsing-remitting multiple sclerosis

The interleukin (IL) -23/IL-17 cytokine axis has been suggested to play an important role in the development of several autoimmune diseases including multiple sclerosis. Here, we compared the prevalence of C2370A single nucleotide polymorphism (SNP) in the 3' untranslated region (3'UTR) of the IL-23 receptor (IL23R) between 223 patients with relapsing-remitting multiple sclerosis (RRMS) and 200 healthy controls. The A2370A genotype was significantly over-represented among patients with RRMS (10.8%) and RRMS exhibiting oligoclonal bands in the cerebrospinal fluid (12.9%) when compared to healthy subjects (5.50%). Multiple regression analysis revealed that presence of AA genotype provides a two-fold risk for the development of multiple sclerosis (OR=2.072, 95% CI: 0.988-4.347, p<0.05). These data indicate that IL23R represents a novel shared susceptibility gene as its association with inflammatory bowel disease (IBD) has recently been verified.     

Exercise, oxidative stress and hormesis

Physical inactivity leads to increased incidence of a variety of diseases and it can be regarded as one of the end points of the exercise-associated hormesis curve. On the other hand, regular exercise, with moderate intensity and duration, has a wide range of beneficial effects on the body including the fact that it improves cardio-vascular function, partly by a nitric oxide-mediated adaptation, and may reduce the incidence of Alzheimer's disease by enhanced concentration of neurotrophins and by the modulation of redox homeostasis. Mechanical damage-mediated adaptation results in increased muscle mass and increased resistance to stressors. Physical inactivity or strenuous exercise bouts increase the risk of infection, while moderate exercise up-regulates the immune system. Single bouts of exercise increases, and regular exercise decreases the oxidative challenge to the body, whereas excessive exercise and overtraining lead to damaging oxidative stress and thus are an indication of the other end point of the hormetic response. Based upon the genetic setup, regular moderate physical exercise/activity provides systemic beneficial effects, including improved physiological function, decreased incidence of disease and a higher quality of life.     

Increased p53 Expression in the Malignant Transformation of Barrett’s Esophagus is Accompanied by an Upward Shift of the Proliferative Compartment

Neoplastic progression in Barrett’s esophagus (BE) occurs by a multistep process associated with early molecular and morphological changes. This study evaluated cell proliferation and p53 expression and their correlation in the development and progression of esophageal adenocarcinoma. PCNA and p53 expressions were analyzed in biopsy samples by immunohistochemistry including patients with reflux esophagitis, BE, BE with concomitant esophagitis, Barrett’s dysplasia, esophageal adenocarcinoma and a control group without any histological changes. Progressive increase in cell proliferation and p53 expression was found in the sequence of malignant transformation of the esophageal mucosa. While cell proliferation was significantly lower in the control group compared with all other groups, there was no increase in p53 expression of esophageal tissues that were negative for dysplasia. Dysplastic BE tissues revealed significantly higher cell proliferation and p53 expression levels compared to BE, reflux esophagitis or BE with concomitant esophagitis. Both, cell proliferation and p53 expression were significantly higher in adenocarcinoma compared to BE or Barrett’s dysplasia. Interestingly, while just BE with concomitant esophagitis showed significantly higher p53 expression levels than BE, both, BE with concomitant esophagitis and reflux esophagitis revealed significantly higher cell proliferation levels compared to BE. Alterations of cell proliferation and p53 expression showed a strong correlation. Simultaneous activation of cell proliferation and p53 expression strongly suggest their association with esophageal epithelial tumor genesis and particularly, their specific role in the biology of esophageal adenocarcinoma. Quantification of these parameters in BE is thought to be useful to identify patients at higher risk for progression to adenocarcinoma.     

Phages from Genus Bruynoghevirus and Phage Therapy: Pseudomonas Phage Delta Case

The applicability and safety of bacteriophage Delta as a potential anti-Pseudomonas aeruginosa agent belonging to genus Bruynoghevirus (family Podoviridae) was characterised. Phage Delta belongs to the species Pseudomonas virus PaP3, which has been described as a temperate, with cos sites at the end of the genome. The phage Delta possesses a genome of 45,970 bp that encodes tRNA for proline (Pro), aspartic acid (Asp) and asparagine (Asn) and does not encode any known protein involved in lysogeny formation or persistence. Analysis showed that phage Delta has 182 bp direct terminal repeats at the end of genome and lysogeny was confirmed, neither upon infection at low nor at high multiplicity of infection (MOI). The turbid plaques that appear on certain host lawns can result from bacteriophage insensitive mutants that occur with higher frequency (10⁻⁴). In silico analysis showed that the genome of Delta phage does not encode any known bacterial toxin or virulence factor, determinants of antibiotic resistance and known human allergens. Based on the broad host range and high lytic activity against planktonic and biofilm cells, phage Delta represents a promising candidate for phage therapy.     

Increasing propensity to mind‐wander by transcranial direct current stimulation? A registered report

Transcranial direct current stimulation (tDCS) has been proposed to be able to modulate different cognitive functions. However, recent meta‐analyses conclude that its efficacy is still in question. Recently, an increase in subjects’ propensity to mind‐wander has been reported as a consequence of anodal stimulation of the left dorsolateral prefrontal cortex (Axelrod et al., Proceedings of the National Academy of Sciences of the United States of America, 112 , 2015). In addition, an independent group found a decrease in mind wandering after cathodal stimulation of the same region. These findings seem to indicate that high‐level cognitive processes such as mind wandering can reliably be influenced by non‐invasive brain stimulation. However, these previous studies used low sample sizes and are as such subject to concerns regarding the replicability of their findings. In this registered report, we implement a high‐powered replication of Axelrod et al. (2015) finding that mind‐wandering propensity can be increased by anodal tDCS. We used Bayesian statistics and a preregistered sequential‐sampling design resulting in a total sample size of N = 192 participants collected across three different laboratories. Our findings show support against a stimulation effect on self‐reported mind‐wandering scores. The effect was small, in the opposite direction as predicted and not reliably different from zero. Using a Bayes Factor specifically designed to test for replication success, we found strong evidence against a successful replication of the original study. Finally, even when combining data from both the original and replication studies, we could not find evidence for an effect of anodal stimulation. Our results underline the importance of designing studies with sufficient power to detect evidence for or against behavioural effects of non‐invasive brain stimulation techniques, preferentially using robust Bayesian statistics in preregistered reports.     

Maternal overnutrition impairs offspring's insulin sensitivity: A systematic review and meta‐analysis

This systematic review and meta‐analysis aimed to investigate the association between maternal overnutrition and offspring's insulin sensitivity—following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses statement. Studies published in English before April 22, 2019, were identified through searches of four medical databases. After selection, 15 studies aiming to explore the association between prepregnancy body mass index (ppBMI) or gestational weight gain (GWG) of non‐diabetic mothers and their offspring's insulin sensitivity (fasting insulin or glucose level and Homeostatic Measurement Assessment for Insulin Resistance [HOMA‐IR]) were included in the meta‐analysis. Associations of ppBMI and GWG with offspring's insulin sensitivity were analysed by pooling regression coefficients or standardized differences in means with 95% confidence intervals (CIs). Maternal ppBMI showed significant positive correlations with the level of both fasting insulin and HOMA‐IR in offspring (standardized regression coefficient for fasting insulin: 0.107, CI [0.053, 0.160], p < 0.001 and that for HOMA‐IR: 0.063, CI [0.006, 0.121], p = 0.031). However, the result of the analysis on coefficients adjusted for offspring's actual anthropometry (BMI and adiposity) was not significant. Independent from ppBMI, GWG tended to show a positive correlation with insulin level, but not after adjustment for offspring's anthropometry. Offspring of mothers with excessive GWG showed significantly higher HOMA‐IR than those of mothers with optimal GWG (p = 0.004). Our results demonstrate that both higher ppBMI and GWG increase the risk of offspring's insulin resistance, but the effect of ppBMI on insulin sensitivity in offspring may develop as consequence of their adiposity.     

Correction to: Gender Differences in the Association between Cyberbullying Victimization and Perpetration: The Role of Anger Rumination and Traditional Bullying Experiences

International Journal of Mental Health and Addiction - Unfortunately, the original version of this article (Zsila et al. 2018) contained an error. The first moderation model relating to the second...     

The role of exercise in brain DNA damage

Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA, which leads to neuronal death. In this way, DNA damage has been implicated in the pathogenesis of neurological disorders, cancer, and aging. Lifestyle factors, such as physical exercise, are neuroprotective and increase brain function by improving cognition, learning, and memory, in addition to regulating the cellular redox milieu. Several mechanisms are associated with the effects of exercise in the brain, such as reduced production of oxidants, up-regulation of antioxidant capacity, and a consequent decrease in nuclear DNA damage. Furthermore, physical exercise is a potential strategy for further DNA damage repair. However, the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown. In this review, we discuss the influence of exercise on DNA damage and adjacent mechanisms in the brain. We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage.     

A successful strategy for surgical treatment of Boerhaave’s syndrome

Background  

This retrospective single-institution study presents a successful treatment strategy for Boerhaave’s syndrome.     

Our policy in diagnosis and treatment of hydrocephalus

The authors present the policy they have worked out for hydrocephalus patients with special reference to the pressure measurement and test methods and to rCBF, SPECT and transcranial Doppler sonography (TDC) studies. For diagnosis, the protocol proposed by Gjerris and Borgesen was followed in 75 cases: besides other methods (CT, radionuclide cisternography, MRI) the intracranial pressure waves routinely recorded and analyzed by means of ventricular catheters for 24 h. The patients were roughly divided into groups in terms of diagnosis, baseline pressure, compliance, results of infusion tests and of surgery. In 13 patients the investigations were supplemented by rCBF SPECT and in 42 patients by TCD studies before and after CSF shunting or withdrawal to analyze the acute effects on cerebral circulation. Clinical follow-up shows that need for shunting was indicated fairly well by the common results of baseline ICP, compliance and infusion loading. The rCBF SPECT studies revealed a significant increase of the cerebral perfusion at the basal ganglia after shunting while, on the basis of CBF velocity changes three types of vasoregulatory response could be defined with TCD. In our hands, monitoring of the pressure and craniospinal capacity has proved to be a valuable aid in decisions on surgery; however, for a more precise (and beneficial) appreciation of whether surgery is indicated the vasoregulatory responses should also be taken into account in future.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992